The Center for Defining and Treating Specific Learning Disabilities in Written Language has seven broad objectives: (1) Use learning profiles of writing, reading, and oral language skills to identify clear, nonoverlapping cases of 3 well-defined specific learning disabilities in written language (SLDs-WL)-impaired handwriting, impaired word reading and spelling, and impaired reading comprehension and written expression-and then evaluate their construct validity based on their concordance with evidence-based, behavioral markers of genetic and brain differences and differential response to the same specialized instruction, that is, Response to Intervention (RTI) (Project I); (2) Investigate the complexities of learning written English, a morphophonemic orthography, during written language tasks in the upper elementary grades and middle school/ junior high grades for students who do and do not struggle in learning written language (Project II); (3) Examine whether the brain's temporal functional connectivity differs among the three SLDs-WL and between them and normal readers and writers and, if so, whether after specialized instruction any prior differences in connectivity normalize (Project III); (4) Increase knowledge of why some students show persisting difficulties in learning written language in the upper elementary and middle school/junior high grades (grades 4 to 9) (Projects I, II, III, and Service Core B); (5) Advance transdisciplinary knowledge of whether phenotypic, genetic (normal or abnormal allele in specific gene locations), and motivation factors predict behavioral RTI (Project I, Service Core B) and brain RTI for students in general (Project III, Service Core B); (6) Advance knowledge of the language, working memory, biological, and affective influences on RTI by evaluating which of the variables in Objective 5 best predicts behavioral RTI and brain RTI for each of the SLDs-W; and (7) Share the transportable, computerized, specialized instruction for students and professional development for teachers (Project I) with researchers and the community serving diverse populations: Spanish-Speaking English language learners and Native Americans in urban and reservation schools (Service Core B). PUBLIC HEALTH RELEVANCE: Children with undiagnosed and untreated specific learning disabilities affecting written language learning are at greater risk for underachievement in the upper grades, school drop out, failure to graduate from high school and gain access to higher education, and related mental health problems. The proposed multidisciplinary research has practical significance for improving diagnosis and providing more effective services which may lower such risks.